Immediate Antioxidant and Antiplatelet Effect of Atorvastatatin via Inhibition of NOX2
Background—Statins exert an antithrombotic effect in patients at risk of or with acute thrombosis; it has never been investigated if such effect is immediate and if there is an underline mechanism.
Methods and Results—Patients with hypercholesterolemia were randomly allocated to a Mediterranean diet with low cholesterol intake (<300 mg/day; n=15) or atorvastatin (40 mg/day; n=15). Oxidative stress, as assessed by serum NOX2 and urinary isoprostanes, and platelet activation, as assessed by platelet recruitment (PR), platelet isoprostanes and thromboxane (Tx) A2, platelet NOX2, Rac1, p47phox, PKC, VASP, nitric oxide (NO) and PLA2, were determined at baseline and after 2, 24, 72 hours and 7 days of follow-up. In vitro study was also performed to see if atorvastatin affects platelet oxidative stress and activation.Atorvastatin-assigned group showed a significant and progressive reduction of urinary isoprostanes and serum NOX2 along with inhibition of PR, platelet isoprostanes, NOX2, Rac1, p47phox and PKC starting 2 hours from administration. Platelet PLA2 and TxA2 significantly decreased while VASP and NO increased after 24 hours. LDL-cholesterol significantly decreased after 72 hours and further declined after 7 days. No changes were observed in the Mediterranean-diet group. In vitro experiments demonstrated that atorvastatin dose-dependently inhibited platelet NOX2 and PLA2 activation along with inhibition of PR, platelet isoprostanes and TxA2 while increased VASP and NO.
Conclusions—The study provides the first evidence that atorvastatin acutely and simultaneously decreases oxidative stress and platelet activation by directly inhibiting platelet NOX2 and ultimately platelet isoprostanes and TxA2. These findings provide a rationale for the use of statins to prevent or modulate coronary thrombosis.
Clinical Trial Registration Information—clinicaltrials.gov; Identifier: NCT01322711.
- Received January 24, 2012.
- Accepted April 30, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited